The research program in this laboratory aims at elucidating the structures and functions of cell membranes, particularly of the cytoplasmic membrane. One project is concerned with the mechanisms of solute transport. The other, the subject of this application, is concerned with the biochemistry of animal cell surfaces and with the role of cell surface substances (particularly the complex carbohydrates) in diverse biological phenomena in the normal and malignant cell; these phenomena include contact inhibition of growth and motility, differentiation and morphogenesis, growth control, etc. The specific problems under study are intercellular adhesion and cell-cell recognition. Various cell types are being employed, including normal (embryonic, 3T3, BHK, muscle cell lines, etc.) and malignant (mouse teratoma, neuroblastoma, SV40 transformed 3T3, polyoma transformed BHK, etc.). Both the specific and non-specific adhesive properties of these cells are being defined by a new quantitative assay, and the assay is being used in attempts to determine the molecular basis for both specific and non-specific intercellular adhesion. Other approaches to this problem are also being used, including the chemical synthesis of "artificial cell surfaces" (i.e., analogues of complex carbohydrates linked to insoluble matrices), studies on the glycolipid and glycoprotein composition of neuroblastoma cell lines in attempts to correlate these components with their electrical, cholinergic, adrenergic, and adhesive properties (to themselves and to muscle cells), and attempts to isolate mutants defective in cell surface components involved in adhesion. Other studies involve utilization of the synthetic solid substrates in attempts to unequivocally demonstrate the existence of cell surface glycosyltransferases, and to study the sub-cellular localization of these enzymes. These studies have a direct bearing on a broad variety of health- related problems, the most obvious being the problem of carcinogenesis.